Gould Karen A, Strecker Tracy E, Hansen Kimberly K, Bynoté Kimberly K, Peterson Kelli A, Shull James D
Department of Genetics, Cell Biology and Anatomy, 985805, University of Nebraska Medical Center, Omaha, Nebraska 68198-5805, USA.
Mamm Genome. 2006 May;17(5):451-64. doi: 10.1007/s00335-005-0183-z.
Chronic estrogen administration can lead to thymic atrophy in rodents. In this article we report that the Brown Norway (BN) rat is sensitive to thymic atrophy induced by the estrogen diethylstilbestrol (DES). By contrast, DES does not induce significant thymic atrophy in the August x Copenhagen-Irish (ACI) strain. The sensitivity of the BN rat to DES-induced thymic atrophy appears to segregate as an incompletely dominant trait in crosses between the BN and ACI strains. In a (BN x ACI)F(2) population, we find strong evidence for three major genetic determinants of sensitivity to DES-induced thymic atrophy on rat Chromosome (RNO) 10 and RNO2. Genotypes at these loci, termed Esta1, 2, and 3, do not have a significant impact on the ability of DES to induce pituitary tumorigenesis or inhibit growth of these F(2) rats. These data indicate that the genetic factors that control DES-induced thymic atrophy are distinct from those that control the effects of DES on pituitary mass and body mass. The Esta intervals on RNO10 and RNO2 overlap with loci that control sensitivity to radiation-induced thymocyte apoptosis, as well as susceptibility to a variety of allergic and autoimmune pathologies, including allergic encephalitis, arthritis, and glomerulonephritis in rodents. These observations suggest that common genetic determinants may control sensitivity to estrogen-induced thymic atrophy, maintenance of thymocyte homeostasis, and immune function.
长期给予雌激素可导致啮齿动物胸腺萎缩。在本文中，我们报告了棕色挪威（BN）大鼠对雌激素己烯雌酚（DES）诱导的胸腺萎缩敏感。相比之下，DES不会在奥古斯特×哥本哈根-爱尔兰（ACI）品系中诱导显著的胸腺萎缩。BN大鼠对DES诱导的胸腺萎缩的敏感性在BN和ACI品系的杂交中表现为不完全显性性状分离。在一个（BN×ACI）F2群体中，我们发现有力证据表明大鼠第10号染色体（RNO）和RNO2上存在三个对DES诱导的胸腺萎缩敏感性的主要遗传决定因素。这些位点的基因型，称为Esta1、2和3，对DES诱导垂体肿瘤发生或抑制这些F2大鼠生长的能力没有显著影响。这些数据表明，控制DES诱导的胸腺萎缩的遗传因素与控制DES对垂体质量和体重影响的遗传因素不同。RNO10和RNO2上的Esta区间与控制对辐射诱导的胸腺细胞凋亡敏感性以及对多种过敏性和自身免疫性疾病易感性的位点重叠，包括啮齿动物的过敏性脑炎、关节炎和肾小球肾炎。这些观察结果表明，共同的遗传决定因素可能控制对雌激素诱导的胸腺萎缩的敏感性、胸腺细胞内环境稳定的维持以及免疫功能。
